Squamous Cell Carninoma
Early detection and treatment of oral cancer is essential for increasing survival rates. The 5-year survival rate has not improved significantly in the past 30 years. For all stages combined, about 82% of persons with oral cavity and pharynx cancer survive 1 year after diagnosis. The 5-year and 10-year relative survival rates are 59% and 48%, respectively. In whites, the survival rate is approximately 55%, while in blacks, it is only 31%. Oral cancer is the sixth most common cancer worldwide. In the US, it accounts for an estimated 35,000 cases of cancer and about 7,600 deaths annually. Oral cavity cancer constitutes about 17,000 of these cases per year and is more common than cervical or ovarian cancer, Hodgkin’s lymphoma, or leukemia.The average age at diagnosis is 63 years. Approximately 96% of oral cancers are detected above the age of 40, and more than 50% of all cancers occur in persons older than 65. However, recent evidence indicates oral cancers are becoming more prevalent in people younger than 40 years.The lifetime ratio of males to females receiving an oral cancer diagnosis is 2:1, although advancing age changes that ratio to nearly 1:1. However, oral cancers are twice as common in males compared to females. The overall incidence of oral cancers has stabilized, relative to the occurrence of newly diagnosed cancers of all oral sites, with absolute numbers increasing only slightly each year. More than 90% of these oral-pharyngeal cancers are squamous cell carcinomas (SCC). The remainder includes salivary gland tumors, lymphoma, and sarcoma.
Often, these malignancies begin as preneoplastic inflammatory lesions, such as leukoplakia, erythroplasia, and erythroleukoplakia. Leukoplakia is a common oral lesion, appearing as a highly phenotypically variable white patch, and may be associated with tobacco and alcohol use, as well as chronic inflammation. When these and other risk factors are present, the risk of malignant transformation to SCC may approach 17%.These leukoplakia (or other premalignant lesions) may become cancerous, especially if they demonstrate epithelial dysplasia. If epithelial dysplasia is diagnosed, the rate of cancer transformation may become as high as 42%. Alterations in host immunity, inflammation, angiogenesis, and metabolism have been noted as prominent clinical features in oral cancers.
The most common site for oral cancers in both American men and women is the tongue, particularly the side surfaces. Recent data indicate about 37% (7,320:20,010) of all oral cancers, excluding the pharynx, occur on the tongue. However, populations in other parts of the world experience oral cancers differently: in India, buccal mucosa carcinomas are more common, and in Southeast Asia, nasopharyngeal cancer occurs more frequently. Data from the Surveillance, Epidemiology and End Results (SEER) Program demonstrate that 30% of all oral cancers diagnosed in the US between 1985 and 1996 occurred on the tongue, followed by the lip and floor of the mouth. Oral tongue cancers (in the anterior two-thirds) accounted for 53% of tongue cancers. The other oral anatomic sites are the lip (22%), floor of the mouth (13%), salivary glands (12%), buccal mucosa (6%), gingiva (6%), and palate (4%).
Floor of the mouth
Stage at Diagnosis and Survival
Unfortunately, the overall survival rates for oral and pharyngeal cancer have not improved significantly in the past 30 years. Furthermore, only 60% of these patients will survive 5 years following treatment. These statistics are worse for tongue carcinoma: about 33%. In the US, the outcomes are more favorable for whites than blacks (55% vs 31%, 5-year survival rates). Undoubtedly, genetics are significantly involved in the predisposition to cancer; however, socioeconomic status, education, and access to the healthcare system also have an influence. The survival rates for advanced tumors are much lower compared with earlier-detected, localized cancers. At diagnosis, almost 50% of all carcinomas of the tongue have metastasized already. An additional 35% to 40% will do so within 5 years. If all oral cancers were diagnosed and treated early as localized tumors, almost 80% of these patients would have 5-year survival rates. This is a major reason for the importance of early detection and/or prevention of the premalignant lesion from progressing to carcinoma. Unfortunately, very little progress has been made in the past 40 years regarding early diagnosis. Additionally, based on more than 25,000 SEER Program oral/pharyngeal cases for which adequate information was available, advanced tumors outnumbered localized, early oral cancers by 59% to 41%. The lip was the only major site where localized cancers were found more frequently than more advanced cancers. Advances in the treatment of oral cancer have not led to significantly improved survival; therefore, earlier diagnosis is the most important factor in improving oral cancer control and reducing morbidity and mortality.
Etiology and Risk Factors
The etiology of oral cancers appears multifactoral, involving long-term exposure to carcinogenic substances, as well as alterations in host immunity and metabolism, angiogenesis, exposure to chronic inflammation, and possibly other factors that accumulate gradually in a genetically susceptible individual. The carcinogenic changes may be influenced by oncogenes, carcinogens, and mutations caused by chemicals, viruses, irradiation, cigarette smoking, excessive alcohol intake, hormones, diet, and physical irritants.
Reports from the US Surgeon General and others conclude that cigarette smoking is the main cause of cancer mortality in the US, contributing to an estimated 30% of all cancer-related deaths and substantially to head and neck cancers.
Tobacco and Alcohol
The association between cigarette use and oral carcinoma has been firmly established from epidemiologic studies, revealing there are more than twice as many smokers among patients with oral cancers as in control populations. One study found that 72% of more than 400 patients with oral cancers smoked, with 58% using more than one pack daily, demonstrating the high risk for tobacco users.
Tobacco use also increases the already high risk for recurrences of oral cancers as well as second primary oral and pharyngeal cancers. The combined effects of tobacco and alcohol are illustrated in another study of more than 350 patients who had oral cancers and a mortality rate of 31% within 5 years.
Alcohol intake also has been associated with the incidence of oral cancers, especially long-term excessive use. One group of investigators found that 44% of 108 patients with cancer of the tongue and 59% of 68 patients with cancer of the floor of the mouth, palate, or tonsillar fossa had unequivocal evidence of alcoholic cirrhosis. Approximately 75% drank alcohol excessively.
Definitive associations between alcohol-containing mouth rinses and the development of oral cancers have not been established.
Although some studies indicate a potential association with dietary factors and cancer in general, no clear characteristics, such as deficiencies or excesses of nutrients, have been recognized as directly correlating with cancers of the oral cavity.
While the role of viruses in development of oral cancers is not known to cause oral SCC, other head and neck cancers have a defined relationship with viruses. Of the viruses that infect oral tissues, those having oncogenic potential are from two groups: the herpes viruses and papillomaviruses. The human papilloma viruses, especially type 16, are among the most likely candidates to cause oral cancers—at least in part. These viruses seem to be more related to pharyngeal cancer than oral cavity sites.
A comprehensive oral examination of every patient is essential to dental practice and for the early detection of oral cancers or premalignant lesions. The standard-of-care examination includes not only a thorough inspection of every intraoral mucosal surface but also the extraoral head and neck tissues, including lymph nodes. Any mucosal abnormality requires an action plan whether that includes treatment, biopsy, referral, or recall examination, and depends upon the nature of the lesion. Many oral lesions that are ill-defined, varying in appearance, controversial, and poorly understood may be benign but may present changes that could be confused easily with malignancy. Conversely, early malignancy may be mistaken often for a benign lesion. Some lesions are considered premalignant because of their statistical correlation with subsequent associated cancerous changes. It is understandable that a considerable amount of clinical uncertainty is involved in the early detection of malignancy, as well as in the understanding that many of these lesions may not remain benign.
Oral cancers may present clinically with different colors and morphologies. They may appear as leukoplakia (white), erythroplasia (red), and most commonly erythroleukoplakia (red and white). They can also be seen as plaques, macules, ulcers, exophytic papules, nodules or tumors, or granular and/or verrucous lesions. Often, SCCs present with very pleomorphic characteristics—combining several of these features—and may be fissured, indurated, and bleeding.
Signs and Symptoms
During the earliest stages, oral cancers are usually completely asymptomatic or may present with only mild irritation. Pain usually occurs in the later stages when the lesion advances and ulcerates. Therefore, thorough oral examinations are imperative for detection of the earlier asymptomatic lesions. Although the gold standard for diagnosis is a biopsy and histopathologic examination, visual morphologic changes may aid the decision to biopsy. Ulceration indicates that the lesion has penetrated through the lamina propria into the connective tissue. Rarely, a patient may seek initial consultation because of a swelling in the neck, which represents a metastasis from an oral lesion of which the patient may be completely unaware. Although there are always exceptions, the following are common presenting signs of oral carcinoma:
• Erythema: Redness of the mucosa that reflects inflammation, thinness, and irregularity of epithelium, as well as a lack of keratinization.
• Ulceration or erosion: Occurs with the destruction of epithelial integrity, owing to discrepancy in cell maturation and disruption of basal lamina (basement membrane).
• Fissuring: The surface texture of the lesion may exhibit ridges and irregularities that reflect abnormal cell growth.
• Leukoplakia: A white patch on the mucosal surface, reflecting excess epithelial keratin production. Hyperkeratosis is associated often with well-differentiated carcinomatous lesions. Excess keratin also may be produced within the stratified squamous epithelium and can appear as “keratin pearls.”
• Erythroplakia: A red macule, plaque, or exophytic lesion that may look similar to trauma or inflammation but may, in fact, represent early angiogenic activity and premaliganancy. The most common clinical presentation of oral precancerous lesions includes some erythema.
Diagnosis and Management
Patients with leukoplakia or other premalignant lesions and even early SCCs are usually asymptomatic. The lesion is usually discovered by a clinician during a routine examination or by a patient who feels roughness in the mouth. No reliable clinical signs and symptoms associated with oral leukoplakia relate to an accurate prediction of a premalignant or early malignant change. However, even mild symptoms are often suggestive of a dysplastic epithelial alteration or an early invasive tumor. Because the clinical appearance of oral leukoplakia—thick or scant, large or small—does not reliably indicate its biologic potential, clinicians should be suspicious of all white lesions and carefully evaluate and observe these patients. The diagnosis of these lesions must be made by histopathologic evaluation.
Adjunctive Clinical Diagnostic Aids
While not intended to be diagnostic tests, adjunctive clinical diagnostic aids may benefit clinicians and patients alike when choosing between a scalpel or punch biopsy. These aids may enhance oral mucosal examinations and perhaps facilitate the procurement of a biopsy, which is the gold standard for diagnosing oral pathology.
In a recent comprehensive review in the Journal of the American Dental Association, Patton et al concluded uncertainty persists as to whether adjunctive screening techniques actually improve the numbers of oral cancers diagnosed or the mortality and morbidity associated with them.Evidence is insufficient for either supporting or refuting visually based screening adjuncts in dental practice. However, their review concluded there is data supporting the benefits of toluidine blue vital staining.
- Chemiluminescence and Toluidine Blue
- Direct Optical Fluorescence
- Transepithelial Cytologyand Brush Biopsy
Long-term survival and functional results of treatment depend on the tumor stage, histology, and treatment plan.The treatment plan is developed at pretreatment conferences (tumor boards) by multidisciplinary consultants and subsequent patient and family concurrence. Additional important outcome factors include the patient’s nutritional status, general health, tobacco use, alcohol intake, and likelihood of compliance with the rigors of therapy.
Curative treatment modalities can be local surgery with wide margins, radiation, or a combination of both. Chemotherapy may be used with these modalities to enhance cure rates and preserve function, which has led increasingly to organ preservation strategies. If survival of the patient is in question, the choice may be to just employ palliative measures to ensure pain control and quality of life.
Otolaryngologists, radiation oncologists, dentists, and rehabilitation specialists work cooperatively in the treatment process. The side effects of treatment are permanent and diminish oral function. Treatment planning is based on careful cancer staging and selection of therapies, which allows for prognostication and facilitates the reporting of outcomes. Physical examination, open biopsy, or fine-needle aspiration biopsy, as well as radiologic imaging studies that include computed tomography, magnetic resonance imaging, and positron emission tomography, are used to classify and stage.
Most major functional disabilities following treatment are related to the disease volume, the degree of radiation, and/or chemotherapy required for treatment that relates to the postoperative complications, including the extent of mandible or tissue loss, reduction of tongue mobility, caries and loss of dentition, xerostomia, muscle trismus, diminished taste and mastication, risk of osteoradionecrosis, and anesthesia of the oral cavity. To achieve a cure, the treatment plan considers an adequate resection of the tumor and surrounding normal tissue and the addition of the lymphatic drainage, while attempting to preserve as much normal anatomy and physiology as possible.
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